NF Forum

In early May, I travelled to Atlanta to participate in the NF Forum, a bi-annual event sponsored by the Children’s Tumor Foundation (CTF). Held in different cities across the U.S. each year, the NF Forum is a national patient education and family gathering that features NF experts from around the country providing a series of keynote presentations, panels, and sessions on a variety of NF topics such as research advances and current clinical issues. The event included a meeting for clinic coordinators, physicians, genetic counselors, and other healthcare professionals, as well as a series of talks aimed at the NF patient community. I presented a talk on advances in NF treatment and provided an update on our research program’s current cutaneous neurofibroma clinical trial using an investigational drug.  The NF Forum is important for disseminating the most current information about NF and also provides NF patients and their families an opportunity to network and learn from one another.

Clinical Care Guidelines for Adults with NF1 

The American College of Medical Genetics and Genomics (ACMG) has recently spearheaded an effort to produce suggestions for clinical practice for adults with NF1. As part of this effort, the ACMG convened a panel of clinical experts to review current practice and published papers, and to use these to formulate guidelines for care of adults with NF1. Concluding many months of work, these guidelines were recently published in the journal Genetics in Medicineand are officially sponsored by the American College of Medical Genetics and Genomics (  These consensus guidelines were written for the professional community, specifically general practitioners and other healthcare professionals providing care to adult patients with NF1.  Pediatric guidelines for NF1 produced by the American Academy of Pediatrics (AAP) have been available for many years. The American College of Medical Genetics and Genomics and the AAP have recently partnered in an effort to write updated pediatric guidelines, which are still in process. 

There are two major types of guidelines: evidence-based and consensus guidelines. Evidence-based guidelines are considered more authoritative and are developed through a formal process that involves gathering published, peer-reviewed results of clinical research and reviewing evidence about why a certain approach or treatment is or is not effective.  Evidence-based guidelines carry a great deal of weight, especially with insurance carriers. However, for NF1, our panel didn’t feel that evidence-based guidelines were an option at this point in time.  The primary reason is that there have been very few large, randomized clinical trials for management of NF1 due to the relatively small numbers of individuals with the condition and the significant variability in symptoms and complications. It is easier to conduct large clinical trials for common conditions such as diabetes and cardiovascular disease.  Another obstacle is that a thorough review of evidence is a time-consuming and expensive process, beyond the reach of the organizations sponsoring the guideline development at this time.

Consensus guidelines, like those written for NF1, are developed by convening a group of clinical experts who provide their opinions based on clinical experience as well as a review of evidence from the literature. These guidelines summarize current knowledge of clinical care and propose an approach to diagnosis and management. Because the consensus guidelines for NF1 are intended for general practitioners, they provide guidance in identifying specific problems but don’t address treatment, which would be managed by a specialist. For example, the guidelines address the identification of patients showing signs of a malignant tumor, but they don’t specify how to treat the malignant tumor. 

Guidelines for Malignant Peripheral Nerve Sheath Tumors 

In the next few months, I’ll try to discuss some of the recommendations of the adult guideline panel, and, when it is available, the pediatric guidelines.  To start, I’ll cover one of the issues addressed in the clinical care guidelines, the occurrence of malignant peripheral nerve sheath tumors (MPNST). These malignancies occur in about 10% of people with NF1 and represent one of the few life-threatening complications of the condition. MPNSTs occur mostly in teens and young adults with NF1. Malignant peripheral nerve sheath tumors usually arise from pre-existing plexiform or nodular neurofibromas. Atypical neurofibromas, which have distinctive clinical and pathological features, may be a precursor to the development of an MPNST and appear as homogenous nodules that, if superficial, have a firm consistency when palpated. 

Because MPNSTs are very difficult to treat, the focus is on early diagnosis. The clinical care guidelines for NF1 indicate a possible diagnosis based on any one of the following: persistent unexplained pain; rapid growth of a tumor; a change in a tumor from soft to hard; and the use of PET scanning to determine increased uptake of the radioactive tracer. The use of whole body MRI may be of value as a screening tool in helping to identify atypical neurofibromas so they can be followed or surgically removed to prevent their progression to MPNSTs. However, the utility of this approach requires further study at this time.

Re-Cap of Successful NF Symposium

Another successful and informative UAB NF Symposium, also known as NF Family Day, was held earlier this month in the Bradley Lecture Center of the Children’s Harbor Building. Co-sponsored by UAB and the Children’s Tumor Foundation (CTF), this half-day, free event provided an opportunity for NF patients and families to hear a series of presentations on a range of NF-related topics from clinical experts. We were pleased to host more than 70 attendees from several states, including as far away as Colorado. A special program of activities was provided for the children in attendance by NF Clinic staff as well as students in the UAB Genetic Counseling and Biomedical Sciences Programs. For the first time, this year’s event featured a keynote speaker from outside the UAB community, New York University neuro-oncologist Kaleb Yohay, M.D., who gave a presentation about the role of alternative medicine in the management of NF. This topic is of great interest to many of our patients, who often ask about the possible benefits of alternative medicine treatments. While alternative medicine is not known to be effective in shrinking tumors or slowing their growth, in some cases there could be some benefits in managing symptoms of NF that can impact quality of life. UAB Professor of Pediatrics and Director of Neuro-Oncology Alyssa Reddy, M.D., provided an update of NF-related clinical trials currently in progress, and I gave a presentation about recommended clinical management for all three forms of neurofibromatosis. In addition to serving as a forum for educating NF patients, families, and the community about important NF-related topics, the event also provides a means for establishing a connection with other NF families who are sharing the same journey. Several NF patients and family members shared how they came to be diagnosed and their personal experiences of managing care for themselves or loved ones. 

Frequency of NF Clinic Visits

Next, I’d like to address a question that patients frequently ask, which is how often should an individual with NF be seen in a specialty NF clinic? I generally recommend that children be seen in clinic on a regular basis, usually once a year.  The rationale for recommending clinic visits for children annually is to help in the identification of any NF-related problems during a period of rapid change as a child develops.  In early childhood, there is uncertainty about how NF will evolve, with the potential for the development of complications such as optic glioma, scoliosis, and bone dysplasia.  For this reason, I recommend that children should be seen once a year by both an NF specialist and a pediatric ophthalmologist.  Of course, if there are recognized problems, it may be appropriate to see a child more than once a year; that should be decided by the physician, together with the family.  

Annual review in an NF Clinic can also be recommended for adults with NF.  Again, the exact frequency of visits depends on the nature of the clinical problems facing the individual.  Some have active problems that require more frequent follow-up; others have been stable for a long period of time, with little change from year-to-year.  In the latter instance, one can debate whether annual follow-up is really necessary.   I can’t say that a rigid annual schedule is critical for all adults with NF1 if nothing is changing clinically.  There are, however, advantages to regular follow-up. First, sometime these visits provide an opportunity to review symptoms that may have been present for a while, but weren’t severe enough to warrant a special visit.  Probably most of these are not medically significant, but sometimes complaints such as pain require further investigation to rule out problems such as malignant change of a neurofibroma.  We do occasionally see people with NF after a gap of many years who have developed significant complications that ideally would have been identified earlier.  A second reason to consider annual follow-up is to stay up-to-date on new advances in the field.  For example, we now have access to clinical trials and even prescription medications that didn’t exist even a few years ago.  The field is changing rapidly, and there is value to staying in touch, as something that couldn’t be treated years ago may well be treatable going forward. A third reason is to provide updated education on NF, including things to look for that might be a sign of progression of the condition.  NF can be a complicated condition, so hearing about the major signs repeatedly over a period of years can be helpful.  Finally, regular – not too frequent, but regular – visits provide a way to stay in touch with the medical team, so that they are familiar with a person’s history if problems do eventually arise.

Our goal is to help patients to be more proactive about their own care and encourage them to stay in touch with their NF care team through tools such as the UAB patient portal when concerns arise.  Also, we’re currently working to develop an educational app that will help patients better understand their condition and signs of potential problems.   The key for successfully managing NF is to remain vigilant about potential problems as much as possible. 

Identifying Areas for Improving Patients’ Clinic Experience

A primary focus of our NF Clinic this year is conducting a careful evaluation of our internal systems to identify areas for improvement. To that end, we have begun a series of internal discussions about process improvements in the clinic with the goal of making the experience of our patients as positive as possible. While we feel that our clinic provides the highest level of care comparable to or better than specialty clinics anywhere in the world, we’re continually interested in identifying areas where we can improve the experience of our patients. Providing comprehensive care for NF patients involves multiple appointments with many specialists as well as coordination of a variety of laboratory and imaging tests. In addition, obtaining insurance preauthorizations requires significant behind-the-scenes work from our staff.

Because of this complexity of care, our ongoing focus is to provide the most streamlined and stress-free experience possible for our patients – and we know that we have to go some distance to achieve this goal. We feel that helping patients to become more engaged in their care is an important way to give them more control and enhance their overall experience. One way we’re doing this is to encourage patients to use the online UAB Patient Portal, which allows secure messaging of clinical information for pediatric and adult patients. This important tool helps to streamline care by expediting and increasing communication between patients and the clinical care team. Although we send electronic invitations to all patients for the portal, not everyone registers to use it because the invitation is sometimes not recognized or the instructions aren’t well understood. We’re focused on increasing usage of the online patient portal system by walking patients through the portal registration process while they are in clinic, as we feel all of our patients can benefit from this care management tool. Additionally, we’re attempting to minimize the number of no-show appointments in our clinic through appointment verifications and other measures.  When a patient doesn’t arrive for an appointment, this represents a slot we could have offered to someone else who was hoping to be seen sooner.   We welcome comments regarding additional ways we can improve our patients’ experience, and we look forward to maintaining our commitment to providing the highest level of patient-centered care.

Atypical Neurofibromas and Malignant Peripheral Nerve Sheath Tumors

Next, I’d like to address the issue of atypical neurofibromas and their potential to become  malignant peripheral nerve sheath tumors (MPNST), probably the most feared complication of NF1. Occurring in about 10% of people with NF1, the malignant peripheral nerve sheath tumor can develop from a pre-existing plexiform neurofibroma. Diagnosis usually requires imaging, and in some cases use of a radioactive tracer (PET scan), and, ultimately, surgical biopsy of the tumor. Surgical resection is the most effective treatment, as these tumors are not sensitive to standard chemotherapy or radiation.  The best way to prevent serious complications resulting from these tumors is to identify them as early as possible and consider surgical resection if this can be done safely.

Atypical neurofibromas, which have distinctive clinical and pathological features, may be a precursor to the development of a malignant peripheral nerve sheath tumor. They usually appear as homogenous nodules that, when palpated, have a firm consistency that is unlike plexiform neurofibromas, which are usually soft or spongy to the touch. Biopsies of atypical neurofibromas tend to show densely packed cells and may show dividing cells, whereas non-malignant neurofibromas typically are less dense.  There is evidence that atypical neurofibromas may be early precursors to a malignant peripheral nerve sheath tumors, so vigilance is important, which may include biopsy or surgical resection.  Whole body MRI is beginning to emerge as a method that may be helpful in identifying atypical neurofibromas, and we are exploring the utilization of whole body MRI for this purpose.